Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis.
Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis.
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DOI：
10.4049/jimmunol.1002653
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Kollnberger S
中科院分区：
文献类型：
--
作者：
Bowness P;Ridley A;Shaw J;Chan AT;Wong-Baeza I;Fleming M;Cummings F;McMichael A;Kollnberger S
CD4辅助T细胞产生促炎细胞因子il - 17 （Th17）与包括脊椎关节炎在内的许多炎性关节炎有关。Th17的发育是由IL23促进的。强直性脊柱炎（AS）是最常见的脊柱炎，与HLA-B27 （B27）和il - 23受体多态性在遗传上相关，但这种联系仍未得到解释。我们之前已经证明B27可以形成重链二聚体（称为B272），与传统的HLA-B27不同，B27可以结合杀伤细胞免疫球蛋白样受体KIR3DL2。本研究表明，表达b272的抗原提呈细胞刺激了脊椎关节炎（SpA）患者血液和滑液中KIR3DL2+ CD4 T细胞的存活、增殖和IL17的产生。尽管在SpA患者的外周血中，KIR3DL2+细胞平均仅占CD4 T的15%，但与对照组相比，该亚群占SpA受试者中观察到的Th17数量增加的70%。来自SpA患者的tcr刺激的外周血KIR3DL2+CD4 T细胞系分泌的IL17比来自对照组的KIR3DL2+细胞系或KIR3DL2阴性CD4 T细胞系多4倍。引人注目的是，KIR3DL2+CD4 T细胞占外周血CD4 T细胞IL23受体表达的大部分，并且在IL23存在时产生更多的IL17。我们的研究结果将HLA-B27与IL-17的产生联系起来，并为AS/SpA提供了新的治疗策略。
CD4 helper T cells producing the pro-inflammatory cytokine IL17 (Th17) have been implicated in a number of inflammatory arthritides including the Spondyloarthritides. Th17 development is promoted by IL23. Ankylosing Spondylitis (AS), the commonest Spondyloarthritis, is genetically associated with both HLA-B27 (B27) and with IL23 receptor polymorphisms, however the link remains unexplained. We have previously shown that B27 can form heavy chain dimers (termed B272), which, unlike classical HLA-B27, bind the Killer-cell Immunoglobulin-like Receptor KIR3DL2. Here we show that B272-expressing antigen presenting cells stimulate the survival, proliferation and IL17 production of KIR3DL2+ CD4 T. KIR3DL2+ CD4 T cells are expanded and enriched for IL17 production in the blood and synovial fluid of patients with spondyloarthritis (SpA). Despite KIR3DL2+ cells comprising a mean of just 15% of CD4 T in the peripheral blood of SpA patients, this subset accounted for 70% of the observed increase in Th17 numbers in SpA subjects compared to controls. TCR-stimulated peripheral blood KIR3DL2+CD4 T cell lines from SpA patients secreted four fold more IL17 than KIR3DL2+ lines from controls or KIR3DL2-negative CD4 T. Strikingly, KIR3DL2+ CD4 T cells account for the majority of peripheral blood CD4 T cell IL23 receptor expression and produce more IL17 in the presence of IL23. Our findings link HLA-B27 with IL-17 production and suggest new therapeutic strategies in AS/SpA.
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DOI：
10.1084/jem.20030896
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Murphy CA;Langrish CL;Chen Y;Blumenschein W;McClanahan T;Kastelein RA;Sedgwick JD;Cua DJ
通讯作者：
Cua DJ
影响因子：
--
作者：
Ciccia, Francesco;Bombardieri, Michele;Triolo, Giovanni
通讯作者：
Triolo, Giovanni
影响因子：
3.6
作者：
Blanco-Gelaz, M. A.;Suarez-Alvareza, B.;Lopez-Larrea, C.
通讯作者：
Lopez-Larrea, C.
影响因子：
5.4
作者：
Kollnberger, Simon;Chan, Antoni;Bowness, Paul
通讯作者：
Bowness, Paul
影响因子：
32.4
作者：
Peh, CA;Burrows, SR;McCluskey, J
通讯作者：
McCluskey, J